Sirtuins and inflammation: Friends or foes?

Abstract

Lysine acetylation/deacetylation has been recognized as an important posttranslational modification regulating numerous cellular processes. Sirtuins represent novel players in these complex regulatory circuits. These NAD-dependent lysine-deacetylases have attracted much interest based on their role in the regulation of lifespan in lower organisms, and their capacity to interfere with cell growth, proliferation and survival in response to stress. Their absolute requirement for NAD suggests that these enzymes may represent an important molecular link between metabolism and several human disorders such as diabetes and cancer. More recently, the identification of several transcription factors known to play a role in the immune system as sirtuin substrates has suggested that this family of enzymes may also play an important role in the regulation of inflammation, a pathological situation with clear links to metabolism and ageing in humans. We review herein the possible links between nuclear sirtuins and the regulation of an immune response, and discuss the possible strategies that may lead to the development of novel therapeutic approaches to treat inflammation by targeting sirtuin activity.

Regulation and function of SIRT1 in rheumatoid arthritis synovial fibroblasts

“…The function of SIRT1 in inflammation is controversial. SIRT1 was shown to regulate many anti-inflammatory processes, but also some pro-inflammatory pathways [43,44]. The anti-inflammatory effect of SIRT1 and also of SIRT6, which we previously found to be induced by smoking, was shown to be mediated by inhibition of NF-kB-dependent gene expression in other cell types [34, 45,46].…”

SIRT3 gene expression: A link between inherited mitochondrial DNA variants and oxidative stress

“…In addition, a wide range of cellular activities attributed to sirtuins is the basis for their involvement in several pathologies, including metabolic, cardiovascular and neurodegenerative diseases, inflammation and cancer (Alhazzazi et al, 2011;Gallí et al, 2011;Guarente, 2007;Haigis and Sinclair, 2010;Huber and Superti-Furga, 2011;Yamamoto et al, 2007). Recently, it was demonstrated that the activity of sirtuins is critically regulated by NAD + biosynthesis.…”

Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity

“…This very diverse set of modifications include phosphorylations, acetylations, sumoylations, ubiquitinations, ADP-ribo-sylations, nitrations and many others (Galli et al, 2011). PT modifications are highly dynamic processes and most of them result from the activity of antagonizing enzymes (e.g., kinases vs. phosphatases, acetylases vs. deacetylases, etc.).…”